Abstract
Publisher Summary The emerging technologies of functional and anatomical brain imaging are finding more frequent application in the study of brain structural abnormalities that may underlie the etiology of schizophrenia. New insight into the role of the regional distribution and receptor binding of anti-psychotic agents has been brought by noninvasive radioimaging techniques. Studies of the blood flow in the brains of schizophrenic patients, with positron emission, have revealed an over-activation in the left hemisphere during the performance of a spatial line orientation test. Positron emission tomography (PET) scanning with oxygen-15 (half-life 123 s) in some schizophrenic patients failed to support the hypothesis of reduced blood flow in frontal cortex. Haloperidol-induced dopamine (DA) receptor supersensitivity in schizophrenics appears to be attenuated by concurrent treatment with lithium. The DA hypothesis of schizophrenia has been reviewed in the light of the recent findings. Perioral dyskinesias can be induced acutely in rats by the DA antagonists' spiroperidol and sulpiride and by the selective agonist SKF 38393. Attempts to separate the multitude of effects shown by cyproheptadine have included the introduction of nuclear substituents and replacement of a benzene ring by a pyrrole ring. The conformational flexibility was higher for these new pyrrolo-compounds than for the corresponding cyproheptadine derivatives as evidenced from the rates of racemization of the atropisomers. SCH 23390, a selective D 1 antagonist, potently reverses d-amphetamine-induced suppression of two specific DA neuronal firing in the chloral hydrate anesthetized rat. This may be a consequence of a nonselective D 2 antagonist effect of the 5-HT 2 receptor antagonist properties of the molecule. This chapter describes the accumulated experience with depot neuroleptics, such as clopenthixol decanoate and pipotiazine palmitate. The anti-hallucinator effect of chlorpromazine correlates with serum levels of prolactin consistent with the DA hypothesis of schizophrenia. No regional sites pecificity for limbic areas were found with thioridazine or with clozapine. The chapter also discusses the anti-psychotic agents through phenothiazines and related rigid compounds, diphenvlpiperidines and butyrophenones, substituted benzamides, and miscellanious compounds.
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